Diabetes mellitus is a chronic disorder of fat, carbohydrate, and protein metabolism. It is characterized by high levels of blood glucose resulting from defects in insulin production, insulin action, or both, which translates into impaired glucose transport and metabolism, resulting in hyperglycemia. The World Health Organization (WHO) estimates that over 180 million people suffer from diabetes, making it one of the most common noncommunicable diseases, and is expected to double by the year 2030.
In the United States, 20.8 million people, or approximately 7% of the population, have diabetes. An estimated 14.6 million have been diagnosed with diabetes, however, 6.2 million are unaware that they have the disease. Over 10% of adults (age 20 or older) have diabetes, while over 20% of Americans age 60 or older have the disease. Approximately 90-95% of all people diagnosed with diabetes have adult-onset, or Type 2 diabetes. The remaining 5-10% of people with diabetes (generally children and young adults) have insulin-dependent, or Type 1, diabetes. The risk of developing diabetes increases with age and body weight, commonly measured by body mass index. About 1.5 million new cases are diagnosed in adults each year. In 2002, diabetes was the sixth leading cause of death in the United States and was very likely to have been underreported. There are serious medical complications that result from having diabetes including heart disease, stroke, high blood pressure, eye complications (retinopathy, cataracts), kidney disease (nephropathy), nervous system disease (neuropathy), peripheral vascular disease, dental disease, gastroparesis, sexual dysfunction, and complications during pregnancy. Overall, the risk of death among age-matched people with diabetes is about twice that of people without diabetes.
People with Type 1 diabetes must have insulin replacement, either delivered by a pump or injection. Those with Type 2 diabetes may be able to control their blood glucose by following a careful diet and exercise program, weight loss, and/or taking oral medications. Many people with diabetes also need to take medications to control their cholesterol and blood pressure. Among adults with diagnosed diabetes, about 11% take both insulin and oral medications, 22% take insulin only, 49% take oral medications only, and 17% do not take either insulin or oral medications. Most non-insulin therapies are oral drugs designed to either lower blood glucose levels, improve the sensitivity to or increase the pancreatic secretion of insulin to postprandial glucose levels. Oral anti-diabetics account for about 63% of the total anti-diabetic drug sales. Metformin, for example, works by keeping the liver from making too much sugar, but is not efficacious for everyone, and effectiveness typically decreases over time. Another class of drugs, insulin-sensitizers or glitazones, lower insulin resistance to help a diabetic's declining levels of insulin to be more effective. However, glitazones have been associated with liver toxicity and death, so physicians remain cautious about the use of these drugs. Accordingly, there is a vast clinical need for safer and more effective therapies to treat diabetes and other related disorders.